Replenishable stent and delivery system

ABSTRACT

Apparatus and a method for treating an irregularity in a wall of a vessel of a patient defined by an irregular or afflicted wall portion with adjacent normal wall portions comprises a catheter having a distal end portion for being guided through the vessel to the site of the irregularity. A balloon associated with said distal end portion of the catheter for selective inflating to contact the walls of the vessel urges a stent carried by the distal end portion of the catheter in a constricted condition for passage through the vessel into an expanded form with the stent spanning the afflicted wall portion and contacting the adjacent wall portions. The catheter is formed with lumens for inflating the balloon, for receiving a guidewire for guiding the catheter through the vessel, and for connecting a port in the catheter proximate the afflicted wall portion to enable delivery of a therapeutic agent into the vessel to contact the stent and the irregular wall portion.

CROSS REFERENCE TO RELATED APPLICATION

[0001] This is a continuation in part of copending application Ser. No.0/507,244 filed Jul. 27, 1995 for a Stent and Therapeutic DeliverySystem which is a continuation of Ser. No. 08/268,999 filed Jun. 30,1994 for a Stent and Therapeutic Delivery System (now U.S. Pat. No.5,439,446 granted Aug. 8, 1995) which applications are all assigned tothe same assignee as the present invention.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention generally relates to stents positionablewithin the body of a patient and more particularly relates to a stentfor delivering a therapeutic agent therefrom and a method and system fordelivery of a therapeutic agent to replenish the stent.

[0004] 2. Description of Related Art

[0005] Physicians often use medical guidewires and catheters incombination. Medical guidewires are devices navigable through narrowpassages in the body such as vessels, tubes, ducts, passages and thelike, hereinafter collectively referred to as vessels. A physiciancontrols the position and travel of a mechanism at a proximal endoutside the body. In other applications the physician guides thecatheter through a laparoscope or endoscope. Medical catheters generallycomprise hollow, flexible tubes that convey fluids, such as contrast,embolic, or pharmacological agents, to or from a vessel within a body.

[0006] Typically in transluminal procedures, a physician inserts anddirects a medical guidewire through a vessel in a patient's body. Thephysician monitors the travel of the guidewire by a fluoroscope or otherknown device. Once positioned proximate the desired area, a steeringmechanism is removed from the guidewire and a medical catheter isinserted into the vessel along the guidewire. Other procedures are alsowell known for directing catheters or similar devices into largervessels of the body such as the esophagus.

[0007] Often these catheters include specialized attachments forproviding different treatment modalities. For example, the followingreferences disclose catheters with attachments for administering atherapeutic agent and performing balloon therapy:

[0008] U.S. Pat. No. 4,824,436 (1989) Wolinsky

[0009] U.S. Pat. No. 4,832,688 (1989) Sagae et al.

[0010] U.S. Pat. No. 5,254,089 (1993) Wang

[0011] U.S. Pat. No. 08/105,737 (1993) Lennox et al.

[0012] U.S. Pat. No. 4,824,436 to Wolinsky discloses a multi-lumencatheter having opposed ring balloons positionable on opposite sides ofa plaque formation in a blood vessel. Inflation of the ring balloonsdefine an isolated volume in the vessel about the plaque. Heparin isthen injected into the volume between the ring to assist the body inrepairing the plaque deposit. This patent also discloses a centralballoon which can be employed to rupture the plaque prior to inflationof the ring balloon.

[0013] U.S. Pat. No. 4,832,688 to Sagae et al. discloses a multi-lumencatheter having an occlusion balloon positionable distally of a tear ina vessel wall. Inflating the balloon occludes the vessel and isolates atthe tear. A therapeutic agent, such as heparin or thrombin, injectedfrom the catheter into the volume reduces the risk of thrombosis orrestenosis. The balloon is then deflated and moved adjacent the ruptureand reinflated to repair the ruptured wall by coagulation of bloodthereat.

[0014] U.S. Pat. No. 5,254,089 discloses a balloon catheter having anarray of conduits disposed within the outer wall of the balloon. Theconduits include apertures in the other wall for delivery of medicationsthrough the wall of the balloon into the body of a patient. This type ofballoon is often referred to as a channeled balloon.

[0015] U.S. application Ser. No. 08/105,737 to Lennox et al., disclosescatheters having spaced balloons for treating aneurysms. The inflatedballoons define an isolated volume about the aneurysm. A port connects avacuum source to evacuate the volume and draw the aneurysmal wall towardits ordinary position. Inflating a third balloon with a heated fluid tocontact the aneurysmal wall effects the repair.

[0016] Therapeutic agent and balloon delivery systems must meet certaincriteria. That is, the cross-sectional dimension of the catheter must beminimized to enable transit through the vessel while also havingsufficient dimension to enable fluid flow to selectively inflate anddeflate the balloon, guidewires to pass therein, and therapeutic agentsto flow therethrough for delivery along the catheter. Catheters mustalso have sufficient internal rigidity to prevent collapse of the lumenswhile having sufficient flexibility for passage along vessels.

[0017] The following references disclose stent delivery systems:

[0018] U.S. Pat. No. 4,690,684 (1987) McGreevy et al.

[0019] U.S. Pat. No. 4,922,905 (1990) Strecker

[0020] U.S. Pat. No. 4,950,227 (1990) Savin et al.

[0021] U.S. Pat. No. 5,059,211 (1991) Stack et al.

[0022] U.S. Pat. No. 5,108,416 (1992) Ryan et al.

[0023] U.S. Pat. No. 5,158,548 (1992) Lau et al.

[0024] U.S. Pat. No. 5,234,457 (1993) Anderson

[0025] U.S. Pat. No. 5,242,399 (1993) Lau et al.

[0026] Stent delivery systems, as disclosed by the Lau et al. and Ryanet al. patents, often include a catheter supporting a compacted stentfor transport in a vessel and an expansible device for expanding thestent radially to implant the stent in the vessel wall. After removal ofthe catheter, the expanded stent keeps the vessels from closing.

[0027] The McGreevy et al. patent discloses a stent formed ofbiologically compatible material, such a frozen blood plasma or thelike. According to McGreevy et al., a stent of this type carried by acatheter may be inserted into opposed ends of a ruptured vessel tosupport the separated vessel walls while the ends are bonded together.Once deployed, the heat from the bonding operation and the bodyeventually melt the stent and clear the vessel.

[0028] The Strecker, patent describes a stent and delivery system. Thestent is knitted from metal or plastic filaments and has a tubularstructure. The delivery system includes a balloon catheter and a coaxialsheath. The catheter supports and carries the compacted stent to a sitewithin the body. The sheath covers the stent preventing prematuredeployment and facilitating transit of the stent through passages in thebody. Exposure of the stent by moving the sheath axially with respect tothe catheter and expansion of a balloon urges the stent into contactwith the walls of the vessel. Deflation of the balloon frees it from thestent and enables withdrawal from the vessel of the delivery system.

[0029] In the Savin et al. patent a stent delivery system includes acatheter having an expansible distal portion, a stent carried thereon ina contracted position for expansion thereby and sleeves that overlie theend portions of the stent. The sleeves protect the vessel and the stentduring transit without substantially inhibiting deployment of the stent.

[0030] The Stack et al. patent discloses a stent delivery systemcomprising a catheter for delivering a compressed stent on a balloon ormechanical extension to the locus of a stenotic lesion. The balloon ormechanical extension proximate the distal end expands the stent anddeflation of the balloon or retraction of the mechanical extensionpermits withdrawal of the distal end of the catheter through the stent.The stent comprises bioabsorbable porous material that reduces thelikelihood of embolization and promotes tissue ingrowth in order toencapsulate the stent.

[0031] In accordance with the Anderson patent a stent delivery systemincludes a dissolvable material that impregnates a self-expanding stentin a compacted form. In one embodiment the removal of a sheath exposesthe stent to body heat and liquids so that the material dissolves andthe stent expands into a

[0032] Stent delivery systems used in such procedures generally includecatheters with selectively expansible devices to deliver and expand acontracted “stent” or restraints that can be removed to allow aself-expanding stent to assure an enlarged or expanded configuration.Stents are known and have a variety of forms and applications. Forexample, stents serve as prostheses and graft carriers in percutaneousangioplasty. Stents used as an endoprothesis and graft carriers to whichthe present invention relates usually comprise radially expansibletubular structures for implant into the tissue surrounding “vessels” tomaintain their patency. As is known, such stents are utilized in bodycanals, blood vessels, ducts and other body passages, and the term“vessel” is meant to include all such passages.

[0033] Like the previously described therapeutic agent and balloontherapy systems, stent delivery systems must conform to severalimportant criteria. First, it is important to minimize the transversedimension of the delivery system, so the stent must be capable ofcompaction against a delivery device, such as a catheter. Second, thedelivery system must facilitate the deployment of the stent once locatedin a vessel. Third, the stent delivery system must easily disengage fromthe stent after the stent is deployed. Fourth, the procedure forremoving the delivery system from the body must be straightforward.Fifth, the delivery system must operate reliably.

[0034] It has been found that the administration of therapeutic agentswith a stent can reduce the risks of thrombosis or stenosis associatedwith stents. Stents administered along with seed cells, such asendothelial cells derived from adipose tissue, can accelerate thereformation of an afflicted area. Likewise, tears or other vessel damageassociated with balloon angioplasty can be reduced by a deployed stentused in combination with a therapeutic agent.

[0035] When both therapeutic agent and stent therapies are required, aphysician generally (1) steers a guidewire to the treatment locus, (2)guides a catheter over the guidewire, (3) operates the catheter toprovide the first stage of treatment, (4) inserts an exchange guidewireto the guidewire, (5) withdraws the catheter, (6) guides a secondcatheter over the guidewire, and (7) operates the second catheter toprovide the second stage of treatment. After this, the physicianwithdraws the guidewire, if not previously removed, and the catheterfrom the body of the patient.

[0036] U.S. Pat. No. 5,439,446 to James Barry the inventor of thepresent invention and commonly assigned discloses a stent deliverysystem that incorporates a drug delivery system in the catheter. Thisdevice permits the surgeon to use one catheter to deliver both the stentand the therapeutic agent at a selected site in the patient's body.

[0037] Other references disclose the use of stents that releasetherapeutic agents associated with a deployed stent over time. Forexample U.S. Pat. No. 5,234,457 to Andersen commonly assigned as thisinvention discloses stents impregnated with a gelatin that enables therelease of the stent. It is suggested that the gelatin could entrain atherapeutic agent that dispenses as the gelatin dissolves.

[0038] These references thus provide the ability to deliver stents andtherapeutic agents to an afflicted site within a patient's body and evenenables the dispersion of the therapeutic agent from the stent overtime. However, if additional therapeutic agent is needed at the siteanother catheter must be inserted to deliver the therapeutic agent or bygenerally introducing the additional therapeutic agent to the vesselsuch as by injection in the case of a blood vessel or by bathing theesophagus for example.

[0039] In some cases where a slow release of the therapeutic agent isdesired, as by the release of a therapeutic agent entrained in a gelatinor other hydrophilic or hydrophobic polymers on a stent. Once thetherapeutic agent was delivered, replenishment required one of twoprocedures. In one, a new stent was inserted to be adjacent the oldstent. Sometimes particularly when the area of treatment was displacedfrom the second stent. An alternative that overcame that problem wassubstituting a new stent for the old stent. It is true that percutaneoustransluminal procedures and other procedures involving the insertion ofstent into the body have improved in recent years. Likewise thereduction in the size of the instruments inserted into the patientreduces the risk of damage. However, it is still a fact that eachinsertion and extraction risks further damage to afflicted areas anddamage to otherwise unaffected areas through which the instruments passand can add to patient trauma. Moreover, insertion and withdrawal ofadditional instruments in sequence increases the time of the physician,staff, and medical facility, and the cost of multiple instruments. Thus,reducing the number of instruments and the overall size of theinstruments necessarily inserted and withdrawn from a patient, the stepsrequired by the processes, and the overall size of each of theinstruments is generally preferred.

[0040] Thus, the above-described references generally disclose variousforms stents and delivery systems for treatments or therapies using acatheter in percutaneous transluminal procedures and other internalprocedures. Some combined with stent delivery systems, which may includea balloon for deploying the stent, while others combine balloon therapyand therapeutic agent delivery systems. Still others of the referencesdisclose a stent delivery system combined with a therapeutic deliverysystem or a stent that actually enables the slow release of atherapeutic agent carried by the stent.

[0041] However, none of these references disclose a stent that enableboth the release of a therapeutic agent therefrom and the charging orrecharging of the stent with a therapeutic agent once positioned withinthe body to permit delivery of therapeutic agent to replenish a stent.None provides a structure for improving the efficiency of percutaneoustransluminal procedures and other internal procedures by providing astent for dispensing a therapeutic agent that can receive additionaltherapeutic agents in vivo and a therapeutic agent delivery system forreplenishing the therapeutic agent dispensed from the stent. Nonedisclose a delivery system and method capable of replenishing atherapeutic agent after it has been depleted from an original supply.

SUMMARY

[0042] Therefore, it is an object of this invention to provide a methodand apparatus for stent and therapeutic agent treatments by a stent witha replenishable reservoir of therapeutic agent

[0043] It is another object of this invention to provide a method andapparatus for charging and recharging with a therapeutic agent atherapeutic agent delivery stent positioned within a patient whereby thestent can continue to dispense a therapeutic agent.

[0044] It is another object of this invention to provide a therapeuticagent delivery system adapted for replenishing a therapeutic agentreservoir of a deployed stent.

[0045] Yet another object of this invention is to provide a method andapparatus which enables delivery of a therapeutic agent to an afflictedportion of a vessel in a patient after depletion of an initial volume oftherapeutic agent carried by the stent.

[0046] It is a further object of this invention to provide a method andapparatus for delivering a stent and therapeutic agent to a vessel whichis relatively simple and inexpensive to produce and use.

[0047] In accordance with one aspect of this invention a stent assemblyfor deployment within a patient's body includes a frame that defines astent assembly form. The frame supports a therapeutic agent reservoircharacterized by allowing therapeutic agent to seep from the reservoir.A port connected to the reservoir allows the introduction of thetherapeutic agent into the reservoir subsequent to the deployment of thestent assembly in the patient's body.

[0048] In accordance with another aspect of this invention a stentassembly for deployment within a patient's body includes a frame thatdefines the shape of the stent asembly. A reservoir carried by the framedelivers the therapeutic agent from the stent assembly. A deliverysystem connects to the reservoir means to enable the addition of thetherapeutic agent to the reservoir means in vitro.

BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The appended claims particularly point out and distinctly claimthe subject matter of this invention. The various objects, advantagesand novel features of this invention will be more fully apparent from areading of the following detailed description in conjunction with theaccompanying drawings in which like reference numerals refer to likeparts, and in which:

[0050]FIG. 1 depicts a single passage vessel with an irregularitycomprising a tear in the wall of the vessel;

[0051]FIG. 2 depicts in side elevation an embodiment of a deliverysystem constructed in accordance with this invention for treating theirregularity in the vessel of FIG. 1 at a first stage in a treatmentmodality;

[0052]FIG. 2A is an enlarged view, partially in cross section, of aportion of a balloon and stent assembly constructed in accordance withthis invention;

[0053]FIG. 3 is a view, partly in schematic and partly in perspectiveform, of portions of the delivery system taken along lines 3-3 in FIG.2;

[0054]FIG. 4 depicts the delivery system of FIG. 2 at an intermediatestage of the treatment modality;

[0055]FIG. 5 depicts a repair vessel and the delivery system of FIG. 2at final stage of the treatment modality prior to its removal from thevessel;

[0056]FIG. 6 depicts in side elevation another embodiment of a deliverysystem similar to FIG. 2 for treating an irregularity the vessel of FIG.1;

[0057]FIG. 7 is a view, partly in schematic and partly in perspectiveform, of portions of the delivery system of FIG. 6 taken along lines 7-7in FIG. 6;

[0058]FIG. 8 depicts in side elevation the embodiment of FIG. 6 at afirst stage in a treatment modality;

[0059]FIG. 9 depicts in side elevation the embodiment of FIG. 6 at anintermediate stage in the treatment modality;

[0060]FIG. 10 depicts in side elevation the embodiment of FIG. 6 at afinal stage of the treatment modality;

[0061]FIG. 11 depicts another embodiment of the delivery system of thepresent invention, similar to those of FIGS. 2 and 6, in the at a firststage in a treatment modality for treating an irregularity in the vesselof FIG. 1;

[0062]FIG. 12 is a view, partly in schematic and partly in perspectiveform, of portions of the delivery system of FIG. 11 taken along lines12-12 in FIG. 11;

[0063]FIG. 13 depicts in side elevation the embodiment of FIG. 11 at afirst stage in a treatment modality;

[0064]FIG. 14 depicts in side elevation the embodiment of FIG. 11 at anintermediate stage in the treatment modality;

[0065]FIG. 15 depicts in side elevation the embodiment of FIG. 11 at afinal stage of the treatment modality; and

[0066]FIG. 16 depicts in side elevation an alternative balloon mountedon a catheter for use in the embodiments of the present invention.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0067]FIG. 1 depicts, in simplified form, a single-passage, tubularvessel 20 through tissue 21, such as peri-arterial tissue, defined by avessel wall 22. Although FIG. 1, and the other similar figures, depict avessel wall as comprising a single homogeneous layer, it will berecognized that an actual vessel wall has multiple layers. However, thisinvention can be understood by referring to the simplified, homogenousrepresentation in the figures. Furthermore it should be appreciated thatthe vessel 20 is intended to be representative generally of any of thediverse passageways found in a patient's body.

[0068]FIG. 1 illustrates an irregularity or abnormality in the wall ofthe vessel 20 at an afflicted or irregular wall portion 23 in the vesselwall 22 that is disposed between essentially normal wall portions 24 and25. In this case, the irregular wall portion 23 includes a flap 23′ thatcan develop due to the weakening and/or stretching of the walls inotherwise normal wall 22. Such flaps frequently result either naturallyor from, for example, stretching by dilation of the vessel duringballoon angioplasty. In the esophagus such tears can result from thepassage of other objects during ingestion or from tumor growth. Tears ofthis kind can also appear in the intestinal tract.

[0069] For ease of understanding the invention, the vessel 20 will bedescribed in terms of a blood vessel. Blood 26 flows in a directionrepresented by arrow 27 within the vessel 20. If left untreated, theflap 23′ can grow in size and occlude the vessel due to coagulation ofblood thereat. Such flaps may also result in ruptures of the vessel.Other abnormalities in vessels of the type to which the presentinvention is applicable include aneurysms, ruptures, stenosis, and thelike. Additionally the stent according to this invention can be used asa site delivery vehicle that over time dispenses a therapeutic agentproximate a desired location such as a tumor, other abnormality or othersite selected for the delivery of such agent.

[0070]FIGS. 2 and 3 depict a delivery system 28 in accordance with thisinvention that includes a medical catheter 30 extending over apredisposed guidewire 31 generally along an axis 32. The catheter 30includes a proximal end portion (not shown) and a distal end portion 34.The distal end portion supports an expansible balloon 35 with anexpandable stent 36 carried in a constricted or compacted condition onthe balloon. It will be understood that various other means forexpanding or enabling the expansion of the stent 36 may be employedwithout departing from the scope of this invention. A plurality oflumens in the catheter 30 include a guidewire lumen 37 through which theguidewire 31 extends and an inflation lumen 38 connecting the balloon 35with a inflation source 39 for selectively inflation and deflation.

[0071] The stent 36 as depicted in FIGS. 2, 2A, 4 and 5 includes pores40 through a frame or structure 40A that defines the overall shape ofthe stent 36 and underlies and supports a membrane 41. The pores orapertures 40 as depicted in FIG. 2A may be provided to promote tissueingrowth as well as to enable flow to or from branches of the vesselconnecting thereat. Those skilled in the art will recognize, however,such apertures may in various procedures be unnecessary or, even,counterproductive. The stent 36 may be formed in other known stentconstructions (e.g., interlocking loops or mesh formed by filaments,etc.) and materials such as various plastic or metals, includingtantalum, stainless steel or nitinol wire that define the frame 40A,provided that the structure defining the stent can support the overlyingmembrane.

[0072] In accordance with this invention a membrane 41 overlies at leasta portion of the frame 40A or preferably as shown in FIGS. 2 and 3 theentire frame. The membrane 41 is permeable to the therapeutic agent anddefines a reservoir or means for enabling the passage or seepage of thetherapeutic agent into the vessel 20 over time. The membrane 41preferably comprises a hydrophilic or hydrophobic polymer with a poresize that enables the therapeutic agent 42 to seep through the membrane41. It will also be recognized that the membrane could be formed ofother materials.

[0073]FIG. 4 depicts the apparatus 28 after the inflation source 39expands the balloon 35 toward the wall 22 of the vessel 20. Expansion ofthe balloon 35 urges the stent 36 into an expanded, deployed conditionso that it spans the irregular wall portion 23 and contacts both theadjacent normal wall portions 24 and 25. Inflation of the balloon 35 inthis case occludes the vessel 20 and defines a portion or volume 51 ofthe vessel that is proximal the balloon 35, the stent 36 and theirregular wall portion 23 and that is relatively isolated from theportion of the vessel distally of the balloon 35. Thus, in thisembodiment the balloon is part of both balloon means associated with thecatheter for selective inflating to contact the walls of the vessel andmeans associated with the catheter for enabling the deployment of thestent in its expanded form.

[0074] Referring again to FIGS. 2 and 3, the catheter 30 has a port 52positioned proximally of the balloon 35. A therapeutic agent source 53and the port are connected by lumen 54 to inject a therapeutic agent 42into the volume 51. In this case, the port 52 and lumen 44 comprisemeans associated with the catheter for delivering a therapeutic agentproximal the inflated balloon and proximate the afflicted wall portionsso that the agent contacts the stent in its expanded form. If themembrane 41 has not previously been charged with therapeutic agent, themembrane tends to absorb the agent. To improve the infiltration of thetherapeutic agent into the membrane, balloons may be provided proximallyand distally of the balloon 35. These added balloons, like balloons 35Pand 35D in FIG. 2A, preserve the isolated volume 51 when the balloon 35deflates. These added balloons, when inflated, can also reduce the sizeof the volume creating an over pressure to further aid in theinfiltration of the therapeutic agent into the membrane 41.

[0075] The therapeutic agent 42 preferably includes an active agent,such as a drug or endothelial cells. Examples of the drugs which wouldbe appropriate active agents include antithrombins such as heparin andderivatives thereof; antiplatelet agents such as PPACK, iloprost,integrelin, and chimeric antibodies such as c7E3; genetic therapiesincluding antisense oligonucleotides and various gene constructs;antipoliferatives such as angiopeptin; chemotherapeutic agents such aspaolitaxel; antioxidants such as probucol; vasorelaxants such asnitroglycerin and papaverine or ones with multiple effects such asnitric oxide; and the like. The active agent would preferably have anaffinity for the afflicted tissue, the stent 35, or both, or the activeagent could be encapsulated or attached to albumin, cells, fibrin andother matrix proteins, platelets, various natural and syntheticpolymers, liposomes, red blood cells or the like having such an affinityif desired. In such case, the active agent, whether directly or due toits encapsulation, would attach on or near the irregular wall portion23.

[0076] If the membrane 41 is formed of a hydrophilic material, andcertain therapeutic agents are introduced into the isolated volume 51,the hydrophilic material initially absorbs a portion of the therapeuticagent. When the bounds on the isolated volume are thereafter removed andthe therapeutic agent in the blood disperses, the hydrophilic membranewill release the absorbed therapeutic agent over time. With such adevice it will be further evident that replenishment can be accomplishedby relocating a balloon such as shown in FIG. 1 in the vessel such thatthe central balloon 35 is located under the stent. The proximal anddistal balloons then would be inflated to form the isolated volume andadditional therapeutic agent could be delivered, with the cyclerepeating thereby a portion of the therapeutic agent would be absorbedin the membrane 41. As an alternative, it would also be possible torecharge the structure through a dual balloon catheter in which twoballoons, such as balloons 35D and 35P in FIG. 2A, form the isolatedvolume inclusive of the membrane. Alternatively a single balloonstructure formed of a channel or other drug delivery type balloon couldbe expanded at the membrane to direct therapeutic agent to the membrane41 for absorption therein.

[0077] Moreover, encapsulating the active agent in a dissolvingmaterial, such as albumin or various polymers which would effect acontinuing release of the active agent proximate the irregular wallportion 23 during the patency of the encapsulating agent. Examples ofsuch polymers would include pluronics gels, citric acid cycle polymers,such as polylactic acid, polyglycolic acid and derivatives thereof,polyanhydrides, polyphosphazenes, polysaccarides, such as alginic acid,chitin and derivatives thereof, collagen and derivatives thereof, andglycosaminoglycans such as hyaluronic acid and derivatives thereof. Inother modalities in which endoscopic procedures are involved, such acatheter as incorporates this invention can be inserted through aworking channel in the ordinary manner and directed to a desiredlocation.

[0078] Use of the present invention to treat irregularities in vesselwalls generally comprises several stages of treatment. The steps usuallyinclude percutaneously inserting the guidewire 31 into a patient'svessel, guiding the guidewire to a position proximate the irregularityin the vessel 20, and inserting the guidewire lumen 37 of the catheter30 over the guidewire 31 to enable the catheter to be directed to theirregularity, as represent in FIG. 2. Once the catheter 30 is positionedproximate the irregularity, the guidewire may be removed or otherwiseremain.

[0079] Notwithstanding the modality used to locate the catheter, oncelocated within a patient, the inflation of the balloon 35 to contact thewall 22 substantially occludes the vessel 20 and inhibits blood flowtherethrough, an depicted in FIG. 4. Inflation of the balloon 35 alsourges the stent 36 from its compacted condition to its expanded,operative condition spanning the afflicted wall portion 23 andcontacting the adjacent normal wall portions 24 and 25. In such a systema number of therapeutic agent delivery procedures could be utilized. Theballoon 35 with its external membrane could be precharged to deliver afirst therapeutic agent while a second therapeutic agent might bedelivered from the source 43 in FIG. 3 thereby to perform two differentdrug therapies simultaneously. Alternatively the membrane could beformed to delay the release of the agent to perform two differentprocedures in sequence. Thereafter the first therapeutic agent or evenanother therapeutic agent capable of being absorbed in the membranecould be applied from the therapeutic agent source 43. In each of thesecases, the deployed stent 36 holds the flap 23′ (see FIG. 2) proximatethe wall of the vessel 20. With the vessel occluded, as depicted in FIG.4, therapeutic agent 42 from the source 43 (FIG. 3) enters the volume 51proximally of the balloon 35 and the stent 36 at the port 52.

[0080] Deflation of the balloon 35, as depicted in FIG. 5, enables thetherapeutic agent 42 to contact the stent 36 and afflicted wall portion23 through the pores 40 and enables retraction of an extreme distal end47 of the catheter through the stent and ultimately from the patient.After the deployment of the stent 36 and deflation of the balloon 35,the catheter 34 may be moved within the vessel to other sites for eitheror both therapeutic agent and balloon therapy. That is, thereafter theballoon 35 serves as a standard inflatable, catheter-mounted balloonwith the port 52 also providing delivery of therapeutic agents asdesired.

[0081]FIGS. 6 and 7 depict another embodiment of this invention asapplied to the vessel 20 with an irregular wall portion 123 comprisingan abnormal narrowing of the vessel or stenosis 123′. A delivery system128 includes a catheter 130 having a distal portion 134. The catheter130 carries the balloon 35 with the stent 36 for deployment within thevessel. The portion 134 also carries an inflatable balloon 137, which inthis instance is positioned distally of the balloon 35, for occluding orsubstantially occluding the vessel. In some cases a second balloon 137′depicted in phantom lines may be positioned opposite the balloon 35 withrespect to the first balloon 137 or even be used in place of the balloon137.

[0082] Referring to FIGS. 6, 7 and 8, a second inflation source 138inflates the balloon 137 into contact with the vessel wall 22 by urginginflating fluid along a lumen 139. The inflated balloon 137 defines avolume 151 in the vessel 20 proximally of the balloon 127 which includesthe wall portion 123. Use of the balloon 137′ would isolate the volume151 about the wall portion 123 in which the stent 36 would bepositioned. The therapeutic agent 42 enters the volume 151 through theport 52 proximally adjacent the balloon 35. As previously discussed withrespect to FIGS. 4 and 5, the therapeutic agent 42 preferably has anaffinity for either or both the afflicted tissue and the stent 36.

[0083] Referring to FIGS. 8 and 9 inflation of the balloon 135 urges thestent 36 from its compacted condition. The deployed, expanded stent 36spans the afflicted wall portion 123 and contacts the adjacent normalwall portions 24 and 25 to urge the stenotic portion 123′ into asubstantially normal position indicated as wall portion 123″.Introduction of the therapeutic agent 42 can occur prior to stentdeployment, during stent deployment or after stent deployment, and theballoon 35 may be reinflated to aid disposition of the agent along thestent 36 and wall 123. Deflation of the balloons 137 and 35, as depictedin FIG. 10, enables retraction of the catheter 130 from the patientwhile the stent 36 remains at the repaired wall portion 123″.

[0084] This embodiment has been described in terms of a four-lumencatheter, although it will be appreciated that various modifications canbe made. For example, the balloons 35 and 137 can be inflated from acommon source through a common lumen when independent inflation is notneeded. Those skilled in the art will recognize that this embodiment canalso be employed as a common angioplastic catheter for treating, forexample, stenotic irregularities by dilation of the vessel proximate thestenosis.

[0085] Specifically, the balloon 137 enables the dilation of vessels todilate a stenotic vessel in a known manner, as well as other therapiesinvolving either or both balloon and therapeutic agent therapies.However, in situations in which an irregularity of the type adapted fortreatment by stent therapy, such as a flap, rupture or otherirregularity results from the balloon therapy or is detected during suchtherapy, in which such irregularity is detected during the balloontherapy, the present invention enables stent and therapeutic agenttherapy without exchanging catheters or other delay. In such case, thecatheter would be repositioned so as to enable the stent to be deployedat the irregular wall portion and the steps previously described wouldoccur. Thus, this embodiment with a separate inflation balloon 137permits a physician to provide balloon therapies, while also providingstent and therapeutic agent therapy as needed.

[0086] In FIGS. 11 and 12 the vessel 20 includes an aneurysmal wallportion 223 with a delivery system 228 for providing therapy foraneurysms positioned proximate thereto. The system 228 includes acatheter 230 having a deployment balloon 235 on which a stent 36 iscarried for deployment.

[0087] As depicted in FIGS. 12 and 13, a vacuum source 231 connectedthrough lumen 232 to port 233 evacuates the isolated volume 151 definedbetween inflated balloons 137 and 137′. Evacuation of the volume tendsto draw the blood 26 from the volume 151 and the aneurysmal wall portion223 toward the catheter 230 proximate the original position of theportion in line with the wall portions 24 and 25, as represented by theportion 223′. The therapeutic agent source injects the therapeutic agent42 into the volume 151 usually after evacuation, although it may alsofollow stent deployment.

[0088] Referring to FIGS. 12 and 14, ionizable fluid 234 directed fromthe inflation source 39 along lumen 38 inflates the balloon 235 tocontact the vessel wall 22 and deploy the stent which may be a standardstent or graft carrying stent. Conductors 251 carried in the lumen 38connect an rf heating source 252 with spaced electrodes 253 and 254 onthe catheter 230 internally of the balloon. The heating source 252energizes the electrodes 253 and 254 with the resulting current betweenthe electrodes 253 and 254 heating the liquid 234 within the balloon235, the stent 35 and the surrounding tissue including the weakenedaneurysmal wall 223.

[0089] This heat thermally coagulates the weakened aneurysmal wall 223.Specifically, thermal coagulation has the chronic effect of formingfibrous scar tissue in the weakened aneurysmal wall 223. This shrinksand thickens the aneurysmal wall 223 to reduce its compliance and arrestprogression of the aneurysm formation which is further strengthened bythe deployed stent 35. Preferable, a temperature sensor 255 connectedthrough the conductors 251 to the rf heating source 252 provides afeedback control signal to accurately regulate the temperature of theliquid 48.

[0090] Upon completion of the treatment with the rf heating source 252deenergized, the vacuum source 45 turned off, and the balloons 137 and235 deflated, the delivery system 228 assumes the compact configurationdepicted in FIG. 15. The blood 26 resumes flow in the direction 127 andthe therapeutic agent 42 not adhering to the stent or wall 123′ flowswith the blood. Next a surgeon removes the apparatus 230 leaving thevessel 20 with a thickened and strengthened wall portion 223′ with astent 36 in place of the aneurysmal wall 223 of FIG. 13.

[0091] Stating that those skilled in the art will now appreciate thatboth with and without the rf heating the embodiment of FIGS. 11 through15 enable a therapeutic agent to be administered and then be withdrawnusing the vacuum source 45. For example, this can be particularly usefulin cases where the therapeutic agent has particular toxic or otheradverse effect on certain tissues of the body. Thus the physician canapply the drug to the affected area and then remove it to minimize anyadverse impact from the therapeutic agent. In a case of an aorticaneurysm after evacuation, the physician can infuse a matrix protein orcollagen to coat the graft for cell adherence in the wall of the graft.The vacuum is then used to suck out the free material. Thereafter,endothelial cells, which may be genetically altered are infused. Thesecells then bond to the protein matrix which preferably promotes cellgrowth and division of the infused endothelial cells.

[0092] The specific apparatus 228 in FIGS. 11 through 15 includes acatheter 230 with five discrete lumens. Certain functions of theselumens may be combined in a single lumen. For example, the vacuum source231 and therapeutic agent source might connect directly to one lumen 44by means of a valve 260. In addition, each of the individual componentsincluding the balloons 137 and the balloon 235 have conventionalconstructions. Apparatus for heating the liquid 234 in the balloon 235through the use of rf energy applied to electrodes 253 and 254 andrelated systems including the temperature sensor 255 are also known inthe art.

[0093] As depicted in FIG. 16, a balloon for deploying the stent neednot fully occlude a vessel 20 and may be combined with the means fordelivering the therapeutic agent. Here, a balloon 35′ mounted on thecatheter 30 in the vessel 20 comprises an inner impermeable layer orsurface 300 and an apertured or otherwise porous layer or outer surface310 (e.g., a channeled balloon). Lumens (not shown), such as lumen 38and 44 of FIG. 3, have ports between the catheter 30 and the innersurface 300 and the surface 310, respectively. Through these lumens, theinflation fluid expands the surface 300 and the therapeutic agent 42 isdelivered interiorly of the outer surface 310. As previously discussed,the stent 36 may be mounted on an expansible balloon, which in thisinstance in the balloon 35′, for deployment.

[0094] Continuing to refer to FIG. 16, the inflation lumen delivers theinflation fluid interiorly of surface 300 to inflate the balloon towardthe walls of a vessel in which the balloon is disposed and to expand astent mounted thereon. The delivery lumen delivers the therapeutic agent42 intermediate the surfaces 300 and 310. Thus, the therapeutic agent 42exits the balloon 35′ through the apertures of the surface 310 tocontact the stent 36 proximate thereto. It will be recognized that theapertured surface 310 comprises a port for the delivery of thetherapeutic agent 42 proximate the stent. Additionally, the apertures inthe surface 310 may be concentrated or entirely positioned in one areaof the balloon 35′. Particularly, the apertures may be provided at theend of the balloon 35′ closest the proximal end of the catheter.

[0095] Those skilled in the art will appreciate that, as discussed withrespect to the embodiment of FIGS. 6 through 10, a second independentinflation balloon may be formed on the catheter 30 of FIG. 16 to providea second means for dilating the vessel thereby. Additionally, theheating means of the embodiment of FIGS. 11 through 15 may also beincluded in either of such balloons, as appropriate for the application.

[0096] The means for expanding and deploying the stent the invention caninclude the stent itself. For example, certain stents react to heat orother conditions by expanding and deploying. Other stents expand anddeploy upon release of a stent from removable sleeves. The apparatusshown in connection with the various figures is adapted for deployingsuch self-expanding stents. A removable sheath is disposed over thestent to protect the vessel and permit selective deployment of thestent. Employing such self-expanding stents eliminates the requirementfor balloon expansion. However, the balloon still functions to occludethe vessel. Alternatively, as shown in FIGS. 11 through 15, thedeployment balloon 35 of FIGS. 2 and 6, for example, can be providedwith electrodes to heat a heat expansible stent to deploy the stent.

[0097] In summary, a delivery system according to each of theembodiments of this invention comprises a catheter having means fordeploying an expandable stent and delivering a therapeutic agent forcontacting the stent. Moreover, the operating techniques are analogousto standard medical procedures with respect to positioning the cathetersin blood vessels, inflating the balloons, deploying the stents, andinjecting therapeutic agents so the use of this apparatus is readilymastered. However, the apparatus eliminates the need for repetitiveinsertion of apparatus for different treatment modalities and reducesthe risk of additional trauma to the patient. The invention alsoimproves the treatment of patients by allowing combined modalities oftreatment relatively concurrently, as well as successively. Theinvention also increases the efficiency of doctors, staff, and medicalfacilities. Moreover, by using bioabsorbable stents no foreign objects,such as clips or tubes, permanently remain permanently in the patientafter treatment. The invention also provides delivery systems sized forthe treatment of irregularities in both large and relatively smallvessels.

What is claimed as new and desired to be secured by Letters Patent ofthe United States is:
 1. A stent assembly for deployment within apatient's body comprising: A. frame means for defining the form of theassembly; B. means supported by said frame means for defining atherapeutic agent reservoir and for enabling the seepage of atherapeutic agent in the therapeutic agent reservoir therefrom; and C.port means connecting with said reservoir means for introducing atherapeutic agent into said therapeutic agent reservoir subsequent todeployment of the stent assembly in a patient's body.
 2. An assembly asrecited in claim 1 wherein said means for defining a therapeutic agentreservoir comprises a porous membrane whereby the therapeutic agentreceived in said membrane seeps through said membrane and into thepatient's body.
 3. An assembly as recited in claim 2 wherein said framemeans comprises an expansible member adapted for insertion in a compactform into the patient's body and for deployment in an expanded form inthe patient's body.
 4. An assembly as recited in claim 3 wherein saidporous membrane overlies said frame means whereby the therapeutic agentreservoir is contiguous with said frame means.
 5. An assembly as recitedin claim 4 wherein said porous membrane comprises a polymeric material.6. An assembly as recited in claim 5 wherein said polymeric material isa hydrophilic polymer.
 7. An assembly as recited in claim 5 wherein saidhydrophobic polymer is a hydrophilic polymer.
 8. An assembly as recitedin claim 1 wherein said frame means comprises an expansible memberadapted for insertion in a compact form into the patient's body and fordeployment in an expanded form in the patient's body.
 9. An assembly asrecited in claim 8 wherein said means for defining the therapeutic agentreservoir overlies said frame means whereby the therapeutic agentreservoir is contiguous with said frame means.
 10. An assembly asrecited in claim 8 wherein said means for defining the therapeutic agentreservoir is formed of a hydrogelic material.
 11. An assembly as recitedin claim 1 wherein said means for defining the therapeutic agentreservoir is formed of a hydrogelic material.
 12. A stent assembly fordeployment within a patient's body comprising: A. frame means fordefining the shape of the assembly; B. reservoir means carried by saidframe means for delivering a therapeutic agent from said stent; and C.delivery means connected to said reservoir means for enabling additionof the therapeutic agent to said reservoir means in vivo.
 13. A stentassembly as recited in claim 12 wherein said frame means comprises anexpansible form for insertion into a patient's body in a compactcondition and for deployment in an expanded condition.
 14. A stentassembly as recited in claim 13 wherein said reservoir means overliessaid frame means.
 15. A stent assembly as recited in claim 14 whereinsaid reservoir means comprises a hydrogelic membrane overlying saidframe means to define thereby a reservoir for receiving the therapeuticagent.
 16. A stent assembly as recited in claim 15 wherein said deliverymeans is a port formed in said membrane.
 17. A stent assembly as recitedin claim 12 wherein said reservoir means overlies said frame means. 18.A stent assembly as recited in claim 15 wherein said reservoir meanscomprises a polymeric membrane overlying said frame means to definethereby a reservoir for receiving the therapeutic agent.
 19. A stentassembly as recited in claim 18 wherein said hydrophilic
 20. A stentassembly as recited in claim 18 wherein said hydrophobic
 21. A stentassembly as recited in claim 16 wherein said delivery means is a portformed in said membrane.
 22. A stent assembly as recited in claim 12wherein said reservoir means includes a hydrogelic membrane supported bysaid frame means to define thereby a reservoir for receiving thetherapeutic agent.
 23. A stent assembly as recited in claim 22 whereinsaid delivery means is a port formed in said membrane.
 24. A therapeuticagent delivery system for replenishing a reservoir of a replenishablestent comprising: A. insertion means having a distal end for insertingwithin the body of a patient and a proximal end for control by anoperator of said insertion means; B. transfer means proximate the distalend of said insertion means for connecting with the reservoir; C. lumenmeans in said insertion means for connecting said transfer means withthe proximal end of said insertion means; and D. means associated withthe proximal end of said insertion means for urging a therapeutic agentthrough said lumen means and transfer means to enable therebyreplenishment of the reservoir of the replenishable stent.
 25. Atherapeutic agent delivery system as recited in claim 24 wherein saidinsertion means comprises a catheter-like tubular member.
 26. Atherapeutic agent delivery system as recited in claim 25 wherein saidtransfer means comprising a fitting corresponding to and mating with afitting connected with the reservoir of the replenishable stent.
 27. Atherapeutic agent delivery system as recited in claim 26 wherein saidproximal end of said tubular member includes a port for replenishing areservoir of a replenishable stent comprising: A. catheter means havinga distal end for insertion within the body of a patient and a proximalend for control by an operator of said cazheter means; B. port meansproximate the distal end of said catheter means for connecting with thereservoir; C. lumen means in said catheter means for connecting saidport means with the proximal end of said catheter means; and D. meansfor urging a therapeutic agent through said lumen means and port meansthereby to replenish the reservoir.
 28. A system comprising: A.insertion means having a distal end for inserting within the body of apatient and a proximal end for control by an operator of said insertionmeans; B. stent means carried proximate the distal end of said insertionmeans in a compact condition for deployment in the body of a patient inan expanded condition, said stent means including: i. frame means fordefining the form of said stent means in the expanded condition, ii.reservoir means for enabling the seepage therefrom of a therapeuticagent disposed in the reservoir, and iii. port means communicating withsaid reservoir means for enabling a therapeutic agent to be insertedinto said reservoir means; C. deployment means carried by said cathetermeans for urging said stent from the compact condition to the expandedcondition to enable selective deployment of said stent; and D. fillingmeans for connecting said port means with a therapeutic agent source toenable insertion of a therapeutic agent into said reservoir means.